Cited by 115Glioma Diagnosis and TreatmentCancer Cells and MetastasisAngiogenesis and VEGF in Cancer

Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature‐on‐a‐Chip System Correlates with Tumor Heterogeneity and Subtypes

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Xiao, Yang, Kim, Dongjoo, Dura, Burak, Zhang, Kerou, Yan, Runchen, Li, Huamin, Han, Edward, Ip, Joshua +6 more·2019·Advanced Science

Published version of a preprint

Abstract

The perivascular niche (PVN) plays an essential role in brain tumor stem‐like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature‐on‐a‐chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single‐cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem‐like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the “homing” of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient‐specific tumor cell functions.

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Authors
Xiao, Y., Kim, D., Dura, B., Zhang, K., Yan, R., Li, H., Han, E., Ip, J., Zou, P., Liu, J., Chen, A. T., Vortmeyer, A. O., Zhou, J., & Fan, R.
Affiliations
  • Yale University (US)
  • Carnegie Mellon University (US)
  • Indiana University Health (US)
  • Yale Cancer Center (US)
Corresponding author
Fan, Rong
Venue
Advanced Science
Publisher
Wiley
Published
2019-02-10
Volume
6
Issue
8
Pages
1801531-1801531
ISSN
2198-3844 (ISSN-L)
OpenAlex
W2913629863
Cited by
115
References
83
Citations by year
2026: 9 · 2025: 12 · 2024: 20 · 2023: 15 · 2022: 20 · 2021: 21 · 2020: 15 · 2019: 3
FWCI
8.08
Type
journal article
Language
en
Open access
Locations
  • Advanced Science (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
  • Publisher
Funders
  • National Science Foundation (CBET‐1351443)
  • National Cancer Institute (U54 CA193461, U54 CA209992)
  • National Institutes of Health (R01 NS095817)
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
glioblastoma, perivascular niche, tumor heterogeneity, tumor cell migration, tumor cell subtypes, proneural subtype, mesenchymal subtype, PDGFRA, single-cell transcriptomics

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